What side effects are associated with this type of intervention?

Common treatments for amyloidosis, particularly RNA-targeted therapies like patisiran and inotersen, often have side effects such as infusion-related reactions, peripheral neuropathy, and gastrointestinal issues. Tafamidis, another treatment, has been associated with similar adverse events to placebo, including cardiovascular-related hospitalizations in severe cases. Diflunisal, used for cardiac manifestations, can cause gastrointestinal discomfort and renal issues. Overall, these treatments aim to stabilize or reduce amyloid deposits but come with a range of potential side effects that need to be managed under medical supervision.

What prior FDA approvals exist?

The FDA has approved tafamidis (Vyndaqel and Vyndamax) for the treatment of transthyretin amyloid cardiomyopathy, which works by stabilizing the transthyretin protein to prevent amyloid formation. Additionally, patisiran, an RNA interference therapy, has been approved for hereditary transthyretin-mediated amyloidosis, reducing transthyretin production by targeting its mRNA. These treatments aim to manage the disease by either stabilizing the protein or reducing its production, similar to the investigational agent vutrisiran being studied for its efficacy and safety in hereditary transthyretin amyloidosis.

What other types of research exist?

Promising alternatives to Vutrisiran for amyloidosis treatment include Tocilizumab (TCZ), Etanercept, and Rituximab. These therapies have shown efficacy in treating various forms of amyloidosis, particularly AA amyloidosis secondary to rheumatic diseases.

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RNAi Therapeutics

Vutrisiran vs Patisiran for Amyloidosis

Phase 3

Waitlist Available

Research Sponsored by Alnylam Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation

Male or female of 18 to 85 years of age (inclusive)

Must not have

Has New York Heart Association heart failure classification >2

Received prior TTR-lowering treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to month 18

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing vutrisiran, an under-the-skin injection, in patients with a genetic condition called hATTR amyloidosis. The medication aims to lower harmful protein levels in their bodies. Vutrisiran is administered as a periodic subcutaneous injection.

Who is the study for?

This trial is for adults aged 18-85 with hereditary transthyretin amyloidosis, a condition where abnormal proteins build up in the body. Participants should have specific levels of neurologic impairment and physical functioning, and not have received other TTR-lowering treatments or had a liver transplant.

What is being tested?

The study compares Vutrisiran, given as an injection under the skin every three months, to Patisiran, administered intravenously every three weeks. After 18 months, participants may receive Vutrisiran less frequently in an extension period.

What are the potential side effects?

Potential side effects include reactions at the injection site for Vutrisiran or infusion-related reactions for Patisiran. Both drugs could potentially cause liver function abnormalities and may affect nerve function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have hATTR amyloidosis with a TTR mutation.

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I am between 18 and 85 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart condition significantly limits my physical activity.

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I have received treatment to lower TTR levels before.

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I have had a liver transplant or might get one during the study.

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I have HIV, HCV, or HBV.

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I have a type of amyloidosis that is not hereditary.

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I have a known cause for my nerve pain or damage.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to month 18

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to month 18

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to month 18 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

Secondary study objectives

Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Vutrisiran + Vutrisiran (HELIOS-A)Experimental Treatment1 Intervention

Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M during the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

Group II: Patisiran + Vutrisiran (HELIOS-A)Active Control2 Interventions

Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once q6M or vutrisiran 25 mg q3M during the RTE Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Amyloidosis, particularly transthyretin (ATTR) amyloidosis, include RNA interference (RNAi) therapies such as Vutrisiran and Patisiran. These treatments work by silencing the gene responsible for producing transthyretin (TTR), thereby reducing the levels of misfolded TTR proteins that form amyloid deposits. This mechanism is crucial for patients because it directly targets the root cause of amyloid formation, potentially stabilizing or even reversing disease progression. Other investigational treatments include gene editing techniques like CRISPR-Cas9, which aim to permanently reduce TTR production. These approaches are significant as they offer targeted, disease-modifying potential, improving outcomes and quality of life for patients with Amyloidosis.

Diagnosis and immunohistochemical classification of systemic amyloidoses. Report of 43 cases in an unselected autopsy series.